A Clinical Study to Assess the Effect of Clopidogrel on the Pharmacokinetics of Selexipag and Its Active Metabolite in Healthy Male Subjects

NCT03496506 | Completed Phase 1

• 1 other identifier: AC-065-117
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the effect of clopidogrel on the pharmacokinetics of selexipag and its active metabolite (ACT-333679) in healthy male adults (by determining the blood concentrations of selexipag and its metabolite). Also, the safety of selexipag when administered alone or with clopidogrel will be assessed.

Conditions

Healthy Subjects

Keywords

selexipag; clopidogrel

Outcome Measures

Primary Outcomes (2)

• Area under the plasma concentration-time profile of selexipag and ACT-333679 during a dose interval (AUC-tau)

  AUC-tau for selexipag and ACT-333679 is calculated on the basis of the actual blood sampling time points drawn during the 12-hour interval after the morning administration of selexipag administered either alone (Day 3) or concomitantly with clopidogrel (Day 4 and Day 10)

  Blood samples at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10 and 12 hours post-dose on Day 3, Day 4 and Day 10

• Maximal plasma concentration of selexipag and ACT-333679 (Cmax)

  Cmax is directly derived from the individual plasma concentration-time curves for selexipag and ACT-333679, following administration of selexipag alone (Day 3) or concomitantly with clopidogrel (Day 4 and Day 10)

  Blood samples at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10 and 12 hours post-dose on Day 3, Day 4 and Day 10

Secondary Outcomes (3)

• Trough plasma concentration of selexipag and ACT-333679 (Ctrough)

  Blood samples from Day 1 to Day 9 before the morning and evening administrations of selexipag and on Day 10 before the morning administration of selexipag

• Time to reach Cmax (tmax)

  Blood samples at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10 and 12 hours post-dose on Day 3, Day 4 and Day 10

• Number of participants with any treatment-emergent adverse events (TEAEs) including serious adverse events

  From the first selexipag administration on Day 1 up to Day 18 (about 1 week after the last administration of selexipag)

Study Arms (1)

Sequential treatment arm

EXPERIMENTAL

Subjects receive 1 tablet of selexipag twice daily from Day 1 to Day 9 and 1 tablet in the morning of Day 10. In the morning of Day 4 and 1 hour before the administration of selexipag, they receive 4 tablets of clopidogrel. Then from Day 5 to Day 10, 1 hour before the morning administration of selexipag, they receive 1 tablet of clopidogrel .

Drug: Selexipag; Drug: Clopidogrel

Interventions

Selexipag DRUG

Each film-coated tablet contains 200 microgram (mcg) of selexipag (oral use)

Also known as: ACT-293987

Sequential treatment arm

Clopidogrel DRUG

Each film-coated tablet containing 75 mg of clopidogrel (oral use)

Sequential treatment arm

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Signed informed consent in the local language prior to any study-mandated procedure.
• Healty male subjects aged between 18 and 45 years (inclusive) at screening.
• Body mass index from 18.0 to 28.0 kg/m2 (inclusive) at screening.
• Systolic blood pressure (SBP) 100-145 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and pulse rate 45-90 bpm (inclusive).

You may not qualify if:

• Any contraindication included in the SmPC of selexipag or clopidogrel treatment.
• History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism or excretion of the study treatments.
• History or clinical evidence of any disorder of hemostasis, hemorrhagic diathesis, nose or gingival bleeding, hemophilia, thrombotic thrombocytopenic purpura, presence of any lesions with a propensity to bleed (particularly gastrointestinal and intraocular), history of bleeding complications after surgical procedures such as tooth extraction
• Previous history of stroke, fainting, collapse, syncope, orthostatic hypotension,vasovagal reactions, head injury.
• Excessive caffeine consumption
• Nicotine consumption within 3 months prior to screening, and inability to refrain from nicotine consumption during the course of the study
• Previous treatment with any prescribed medications (including vaccines) or over the counter (OTC) medications (including herbal medicines such as St John's Wort, homeopathic preparations, vitamins, and minerals) within 2 weeks prior to first selexipag administration.
• Subjects with rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
• Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study or compliance with the protocol.

Sponsors & Collaborators

• Actelion: lead

Study Sites (1)

Clinical Pharmacology Unit (CPU)

Merksem, 2170, Belgium

Location

Related Publications (1)

• Axelsen LN, Poggesi I, Rasschaert F, Perez Ruixo JJ, Bruderer S. Clopidogrel, a CYP2C8 inhibitor, causes a clinically relevant increase in the systemic exposure to the active metabolite of selexipag in healthy subjects. Br J Clin Pharmacol. 2021 Jan;87(1):119-128. doi: 10.1111/bcp.14365. Epub 2020 Jun 5.

  PMID: 32415684 DERIVED

MeSH Terms

Interventions

selexipag; Clopidogrel

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Shirin Bruderer

  Actelion

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, two-treatment, one-sequence, cross-over study

Study Record Dates

• First Submitted: April 6, 2018
• First Posted: April 12, 2018
• Study Start: March 5, 2018
• Primary Completion: May 10, 2018
• Study Completion: May 18, 2018
• Last Updated: June 22, 2025

Record last verified: 2025-06

Locations

BE (1)